Quinolinyl (or pyridinyl) methoxy substituted naphthalene compounds as antiallergic agents

ABSTRACT

There are disclosed compounds of the formula ##STR1## wherein X is --Ch 2  CH 2  --, --CH=CH--, ##STR2## Z is CR or N, when n=1; or Z is O, S, or NR, when n=0; R is hydrogen or loweralkyl; 
     n is 0 or 1; 
     R 1  is hydroxy, amino, loweralkyl sulfonamido, perfluoro loweralkyl sulfonamido or OR; 
     R 2  is hydrogen or loweralkyl; 
     R 3  is hydrogen or loweralkyl; or 
     R 2  and R 3  taken together form a benzene ring; and 
     the dotted line represents an optional double bond; 
     and the pharmaceutically acceptable salts thereof, and their use in the treatment of leukotriene-mediated naso-bronchial obstructive airpassageway conditions, such as allergic rhinitis, allergic bronchial asthma and the like.

This is a continuation-in-part of U.S. Ser. No. 703,788 filed Feb. 21,1985, now abandoned.

This invention relates to novel naphthalene compounds possessinglipoxygenase inhibitory and slow-reacting substance of anaphylaxis(SRS-A) antagonist activity which are useful as anti-inflammatory andantiallergic agents.

It is known that arachidonic acid (AA) is metabolized in mammals by twodistinct pathways. The metabolism of arachidonic acid by cyclooxygenaseenzymes results in the production of prostaglandins and thromboxanes.The physiological activity of these AA metabolites has been amplyelucidated in recent years. The other pathway of AA metabolism involveslipoxygenase enzymes and results in the production of a number ofoxidative products called leukotrienes. The latter are designated by theLT nomenclature system, and the most significant products of thelipoxygenase metabolic pathway are the leukotrienes C₄ and D₄. Thesubstance denominated slow-reacting substance of anaphylaxis (SRS-A) hasbeen shown to consist of a mixture of leukotrienes, with LTC₄ and LTD₄as the primary products and having varying amounts of other leukotrienemetabolites [see Bach et al., J. Immun. 215, 115-118 (1980); Biochem.Biophys. Res. Commun. 93, 1121-1126(1980)].

The significance of these leukotrienes is that a great deal of evidenceis accumulating showing that leukotrienes participate in inflammatoryreactions, exhibit chemotactic activities, stimulate lysosomal enzymerelease and act as important factors in the immediate hypersensitivityreaction. It has been shown that LTC₄ and LTD₄ are potentbronchoconstrictors of the human bronchi [see Dahlen et al., Nature 288,484-486 (1980)], and another leukotriene, LTB₄, is a powerfulchemotactic factor for leukocytes [see A. W. Ford-Hutchinson, J. Roy.Soc. Med., 74, 831-833 (1981)]. The activity of leukotrienes andslow-reacting substances (SRS's) as mediators of inflammation andhypersensitivity is extensively reviewed in Bailey and Casey, Ann.Reports Med. Chem., 17, 203-217(1982).

The biological activity of the leukotrienes and SRS's, and oflipoxygenase as the enzyme leading to the metabolism of AA toleukotrienes, indicates that a rational approach to drug therapy toprevent, remove or ameliorate the symptoms of allergies, anaphylaxis,asthma and inflammation must focus on either blocking the release ofmediators of these conditions or antagonizing their effects. Thus,compounds which inhibit the biological effects of the leukotrienesand/or which control the biosynthesis of these substances, as byinhibiting lipoxygenase, are considered to be of value in treating suchconditions as allergic bronchial asthma, allergic rhinitis, as well asin other immediate hypersensitivity reactions.

The invention provides novel compounds of the formula ##STR3## wherein Xis --CH₂ --CH₂ --, --CH═CH-- or ##STR4## Z is CR or N, when n=1; or Z isO, S, or NR when n=0; R is hydrogen or loweralkyl;

n is 0 or 1;

R¹ is hydroxy, amino, loweralkyl sulfonamido, perfluoro loweralkylsulfonamido or OR;

R² is hydrogen or loweralkyl;

R³ is hydrogen or loweralkyl; or

R² and R³ taken together form a benzene ring; and

the dotted lines represent optional double bonds;

and the pharmaceutically acceptable salts thereof.

The term "loweralkyl" refers to moieties having 1-6 carbon atoms.

The compounds of the invention can be prepared in the following manner;##STR5## wherein Z, n, R¹, R² and R³ are as defined hereinbefore and halrefers to a halo radical, for example, chloro or bromo. The reaction iscarried out in an organic solvent, for instance, dimethylformamide, atreduced temperature under a nitrogen atmosphere. The naphthaleneintermediate in the above reaction sequence can be employed in itsalkali metal derivative form.

Compounds of the invention in which the naphthalene portion of themolecule have the formula: ##STR6## can be prepared as described suprausing a 7-hydroxy-tetralone, followed by reduction of the ketone to thealcohol form, for example: ##STR7## where Z, n, R¹, R², R³ and hal areas defined hereinbefore. The reduction is carried out in an organicsolvent, for example, tetrahydrofuran, under a nitrogen atmosphere.

Compounds in which the naphthalene portion of the molecule have theformula ##STR8## can be prepared as described supra using a7-hydroxy-tetralone, followed by a Wittig reaction: ##STR9## wherein Z,n, R¹, R², and R³ are as defined hereinbefore. The reaction is carriedout in an organic solvent for example, tetrahydrofuran, under a nitrogenatmosphere.

Compounds in which R¹ is loweralkyl sulfonamido can be prepared by theprocedures described hereinbefore, using an appropriateamino-2-naphthol, e.g. the sodio derivative thereof, as the startingintermediate, and in the final reaction step, reacting the resultingamine with a loweralkyl or perfluoro loweralkyl sulfonyl halide:##STR10## wherein Z, n, R², R³ loweralkyl and hal are as definedhereinbefore.

The starting compounds in the above preparative sequences arecommercially available or can be prepared by conventional methods knownin the art.

The compounds of the invention are capable of forming pharmacologicallyacceptable salts, including the salts of pharmacologically acceptableorganic and inorganic acids such as hydrochloric, hydrobromic, sulfuric,nitric, phosphoric, methanesulfonic, benzenesulfonic, acetic, citric,fumaric, maleic, succinic, oxalic and the like.

The compounds of the invention, by virtue of their ability to inhibitthe activity of lipoxygenase enzyme and by their ability to antagonizethe effects of LTD₄ and LTC₄, which are the major constituents of SRS-A,are useful for the inhibition of symptoms induced by these leukotrienes.Accordingly, the compounds are indicated in the prevention and treatmentof those disease states in which LTD₄ and LTC₄ are causative factors,for example, allergic rhinitis, allergic bronchial asthma and otherleukotriene mediated naso-bronchial obstructive air-passagewayconditions, as well as in other immediate hypersensitivity reactions,such as allergic conjunctivitis. The compounds are especially valuablein the prevention and treatment of allergic bronchial asthma.

When the compounds of the invention are employed in the treatment ofallergic airways disorders, they can be formulated into oral dosageforms such as tablets, capsules and the like. The compounds can beadministered alone or by combining them with conventional carriers, suchas magnesium carbonate, magnesium stearate, talc, sugar, lactose,pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodiumcarboxymethylcellulose, low melting wax, cocoa butter and the like.Diluents, flavoring agents, solubilizers, lubricants, suspending agents,binders, tablet-disintegrating agents and the like may be employed. Thecompounds may be encapsulated with or without other carriers. In allcases, the proportion of active ingredients in said compositions bothsolid and liquid will be at least to impart the desired activity theretoon oral administration. The compounds may also be injected parenterally,in which case they are used in the form of a sterile solution containingother solutes, for example, enough saline or glucose to make thesolution isotonic. For administration by inhalation or insufflation, thecompounds may be formulated into an aqueous or partially aqueoussolution, which can then be utilized in the form of an aerosol.

The dosage requirements vary with the particular compositions employed,the route of administration, the severity of the symptoms presented andthe particular subject being treated. Treatment will generally beinitiated with small dosages less than the optimum dose of the compound.Thereafter the dosage is increased until the optimum effect under thecircumstances is reached. In general, the compounds of the invention aremost desirably administered at a concentration that will generallyafford effective results without causing any harmful or deleterious sideeffects, and can be administered either as a single unit dose, or ifdesired, the dosage may be divided into convenient subunits administeredat suitable times throughout the day.

The lipoxygenase inhibitory and leukotriene antagonist effects of thecompounds of the invention may be demonstrated by standardpharmacological procedures, which are described more fully in theexamples given hereinafter.

These procedures illustrate the ability of the compounds of theinvention to inhibit the polymorphonuclear leukocyte synthesis of thelipoxygenase product 5-HETE, and measure the in vivo activity of thecompounds as lipoxygenase inhibitors and leukotriene antagonists ofendogenous mediators of bronchospasm.

The following examples show the preparation and pharmacological testingof compounds within the invention.

EXAMPLE 1 1,2,3,4-Tetrahydro-7-(2-quinolinylmethoxy)-1-naphthalenol A.3,4-Dihydro-7-(2-quinolinylmethoxy)-1(2H)-naphthalenone

To a slurry of NaH (0.29 g, 12.25 mmol) in 25 mL dimethylformamide undernitrogen at 0° C. is added portionwise 7-hydroxy-1-tetralone (2.0 g,12.33 mmol) over 5 minutes. After half an hour,2-(chloromethyl)quinoline (2.2 g, 12.43 mmol) is added in 10 mLdimethylformamide. The ice bath is removed and the reaction mixture isstirred overnight. The solvent is then removed in vacuo and the residueis partitioned between 1N sodium hydroxide and methylene chloride. Theorganic layer is separated, dried over magnesium sulfate, evaporateddown to an oil, and chromatographed on silica gel. Elution with 9-1methylene chloride/ethyl acetate gives 2.0 g(54%). This material isrecrystallized from acetonitrile to afford 1.3 g (35%) of yellowcrystals, m.p. 98.5°-101.5° C.

Analysis for: C₂₀ H₁₇ NO₂ :

Calculated: C, 79.18; H, 5.65; N, 4.62.

Found: C, 79.09; H, 5.65; N, 4.70.

B. 1,2,3,4-Tetrahydro-7-(2-quinolinylmethoxy)-1-naphthalenol

To a solution of 0.62 g (16.33 mmol) lithium aluminum hydride in 80 mLtetrahydrofuran under nitrogen at 0° C. is added dropwise with stirringa solution of 5.0 g (16.48 mmol) of3,4-dihydro-7-(2-quinolinylmethoxy)-1(2H)-naphthalenone over 1 minute.The ice bath is removed and after 1 hour the reaction is worked upaccording to Micovic and Mihailovic¹. The crude product isrecrystallized from ethylacetate/hexane and affords 3.1 g (62%) of whitecrystals, m.p. 113°-115° C.

Analysis for: C₂₀ H₁₉ NO₂ :

Calculated: C, 78.66; H, 6.27; N, 4.59.

Found: C, 79.15; H, 6.23; N, 4.81.

EXAMPLE 2 7-(2-quinolinylmethoxy)-2-naphthalenol

The title compound is obtained by using the procedure of Example 1 forpreparation of the starting material, but using 2,7-naphthalenediol. Theworkup is modified as follows: after removal of the dimethylformamide invacuo, water is added to the residue and the insolubles are filtered offand dried, recrystallized from acetonitrile, the crystals are treatedwith 9:1 hexane/ethyl acetate and the insoluble portion isrecrystallized from acetonitrile to afford white crystals, m.p.218°-220° C. HPLC analysis (μPorasil, 9:1 methylene chloride/ethylacetate) reveals a purity of 98%.

Analysis for: C₂₀ H₁₅ NO₂ :

Calculated: C, 79.71; H, 5.02; N, 4.64.

Found: C, 79.94; H, 4.91; N, 4.83.

EXAMPLE 3 2-[[(7-methoxy-2-naphthalenyl)oxy]methyl]quinoline

The title compound is obtained by using the procedure of Example 1 forpreparation of the starting material utilizing methyl iodide and7-(2-quinolinylmethoxy)-2-naphthalenol. The workup is modified asfollows: after removal of the dimethylformamide in vacuo, water is addedto the residue and the insolubles are filtered off and dried andchromatographed on silica gel (eluant: methylene chloride).Recrystallization from methanol affords white crystals, m.p. 113°-114.5°C.

Analysis for: C₂₁ H₁₇ NO₂ :

Calculated: C, 79.98; H, 5.44; N, 4.44.

Found: C, 80.47; H, 5.45; N, 4.49.

EXAMPLE 4 7-(2-benzothiazolylmethoxy)-2-naphthalenol

The title compound is obtained by using the procedure of Example 1 forpreparation of the starting material utilizing2-(chloromethyl)-benzothiazole and 2,7-naphthalenediol. The workup usedis that of Example 2 up to the first recrystallization where the solventis changed to toluene. Yellow crystals are obtained, m.p. 205°-207° C.

Analysis for: C₁₈ H₁₃ NO₂ S:

Calculated: C, 70.33; H, 4.26; N, 4.56.

Found: C, 70.72; H, 4.30; N, 4.79.

EXAMPLE 5 7-(2-pyridinylmethoxy)-2-naphthalenol

The title compound is obtained by using the procedure of Example 4 butusing methanol as the recrystallization solvent and using2-(chloromethyl)pyridine and 2,7-naphthalenediol. Brown crystals areobtained, m.p. 190°-193° C.

Analysis for: C₁₆ H₁₃ NO₂ :

Calculated: C, 76.48; H, 5.21; N, 5.58.

Found: C, 76.49; H, 5.25; N, 5.57.

EXAMPLE 6 7-(2-quinolinylmethoxy)-1-naphthalenamine

The title compound is obtained by using the procedure of Example 4 using2-(chloromethyl)quinoline and 1-amino-7-hydroxy-naphthalene. Browncrystals are obtained, m.p. 148° C. (dec.).

Analysis for: C₂₀ H₁₆ N₂ O:

Calculated: C, 79.97; H, 5.37; N, 9.16.

Found: C, 80.34; H, 5.38; N, 9.45.

EXAMPLE 7 7-(2-quinolinylmethoxy)-2-naphthalenamine

To a suspension of 40.0 g 7-amino-2-naphthol hydrochloride (205 mmol) in250 mL methanol under nitrogen is added 451 mL of 0.91N sodium methoxide(410 mmol) in methanol. After 1 hour of stirring, the solvent is removedand the residue is taken up in 500 mL dimethylformamide and cooled to10° C. under nitrogen. A solution of 36.3 g 2-(chloromethyl)quinoline(205 mmol) in 200 mL dimethylformamide is added. After stirringovernight at ambient temperature, the reaction is stripped of solvent,water is added and the precipitate is filtered off, dried andrecrystallized from toluene to afford 31.1 g (62%) of white crystals,which is further purified by filtration through Florisil.Recrystallization from toluene affords white crystals, m.p.164.5°-166.0° C.

Analysis for: C₂₀ H₁₆ N₂ O:

Calculated: C, 79.97; H, 5.37; N, 9.33.

Found: C, 80.07; H, 5.33; N, 9.10.

EXAMPLE 8 N-[7-(2-quinolinylmethoxy)-2-naphthalenyl]ethane sulfonamide

A solution of 5.00 g 7-(2-quinolinylmethoxy)-2-naphthalenamine (17mmol), prepared according to the procedure of Example 7, 1.7 gtriethylamine (17 mmol) and 2.18 g ethanesulfonyl chloride (17 mmol) in50 mL tetrahydrofuran is refluxed overnight. The solvent is removed andthe residue is partitioned between methylene chloride and saturatedsodium bicarbonate. After drying over potassium carbonate, the organiclayer is freed of solvent to afford 5.00 g of a brown gum.Chromatography on alumina and elution with 9:1 methylene chloride/ethylacetate affords 1.4 g of a white solid which is recrystallized fromethyl acetate. Rechromatography on HPLC and final recrystallization fromethyl acetate affords 0.6 g (9%) of white crystals, m.p. 166°-167.5° C.

Analysis for: C₂₂ H₂₀ N₂ O₃ S:

Calculated: C, 67.32; H, 5.14; N, 7.14.

Found: C, 67.13; H, 5.18; N, 6.99.

EXAMPLE 92-[[(5,6,7,8-tetrahydro-8-methylene-2-naphthalenyl)oxy]methyl]quinoline

To a suspension of 3.6 g (10.1 mmol) of methyltriphenylphosphoniumbromide in 50 mL tetrahydrofuran under nitrogen at -50° C. is addedn-butyllithium (10 mm as a hexane solution (2.1 M)). After 45 minutes, asolution of 3.0 g (9.90 mmol) of3,4-dihydro-7-(2-quinolinylmethoxy)-1(2H)-naphthalenone, preparedaccording to Example 1A above, in 50 mL tetrahydrofuran is addeddropwise and the reaction mixture is allowed to slowly come to roomtemperature. After three days, 50 mL water and 50 mL ether is added. Theorganic layer is separated, dried over magnesium sulfate and evaporatedto 5.0 g of crude product. Chromatography accords 1.3 g (44%) of thedesired product. Recrystallization from hexane gives 0.70 g (24%) ofwhite crystals mp 56°-58° C.

Analysis for: C₂₁ H₁₉ NO:

Calculated: C, 83.68; H, 6.35; N, 4.65.

Found: C, 83.51, H, 6.38; N, 4.70.

EXAMPLE 10 N-[7-(2-quinolinyl methoxy)-2-naphthalenyl]trifluoromethanesulfonamide

To a solution of 12.0 (40 mmol) of 7-(2-quinolinylmethoxy)-2-naphthalenamine in 200 mL of methylene chloride at 0° C.containing 6 mL (42 mmol) of triethylamine is added 6.8 mL (40 mmol) ofrifluoromethanesulfonic anhydride. The reaction mixture is then allowedto warm to ambient temperature. After stirring overnight, the reactionmixture is washed with water, dried over magnesium sulfate, andevaporated to yield 13.5 g of a brown solid. Trituration with methylenechloride gives 2.7 g of insoluble material which is recrystallized fromtoluene to afford 1.9 (11%) of white crystals, mp. 172°-175° C.

Analysis for: C₂₁ H₁₅ F₃ N₂ O₃ S:

Calculated: C, 58.33; H, 3.50; N, 6.48.

Found: C, 58.48; H, 3.58; N, 6.14.

EXAMPLE 11

The compounds 5- and 12-hydroxyeicosatetraenoic acid (5-HETE and12-HETE) and 5,12-dihydroxyeicosatetraenoic acid (5,12-diHETE) are earlyarachidonic acid oxidation products in the lipoxygenase cascade, whichhave been shown to mediate several aspects of inflammatory and allergicresponse. This is especially true with respect to 5,12-diHETE, which isalso denoted as LTB₄ [see Ford-Hitchinson, J. Roy. Soc. Med., 74, 831(1981)]. The assay of this Example measures the ability of the compoundsof the invention to inhibit the synthesis of 5-HETE by ratglycogen-elicited polymorphonuclear leukocytes.

The array is carried out as follows:

Peritoneal PMN are obtained from female Wistar rats (150-250 g) thatreceived an i.p. injection of 6% glycogen (10 mL). After 24 hours, ratsare killed by CO₂ asphyxiation and peritoneal cells are harvested byperitoneal lavage using Ca⁺⁺ and Mg⁺⁺ free Hanks' balanced salt solution(HBSS). The peritoneal exudate is centrifuged at 400 g for 10 minutes.After centrifugation, the lavaged fluid is removed and the cell pelletis resuspended in HBSS containing Ca⁺⁺ and Mg⁺⁺ and 10 mM L-cysteine ata concentration of 2×10⁷ cells/mL. To 1 mL portions of cell suspension,test drugs or vehicle are added and incubated at 37° C. for 10 minutes.Following this preincubation, the calcium ionophore (10 μM), A23187, isadded together with 0.5 μCi [¹⁴ C] arachidonic acid and furtherincubated for 10 minutes. The reaction is stopped by the addition of icecold water (3 mL) and acidifying to pH 3.5. Lipoxygenase products arethen extracted twice into diethyl ether. The pooled ether extracts areevaporated to dryness under nitrogen and the residue is redissolved in asmall volume of methanol and spotted on aluminum backed pre-coated thinlayer chromatographic plates. The samples are then co-chromatographedwith authentic reference 5-HETE in the solventsystem-hexane:ether:acetic acid (50:50:3). After chromatography, theareas associated with 5-HETE standard are identified by autoradiography,cut out and quantitated by liquid scintillation.

Results are expressed as % inhibition of [¹⁴ C]5-HETE synthesis.##EQU1##

Testing compounds of the invention in this assay the following resultsare obtained, where the concentration of the compounds tested is 50 μMunless otherwise stated.

                  TABLE I                                                         ______________________________________                                        Compound of                                                                   Example Number                                                                              % Inhibition of 5-HETE                                          ______________________________________                                        1             >50                                                             2             >50                                                             3             >50                                                             4             >50                                                             5             >50                                                             6             >50                                                             7             >50                                                             8             >50                                                             9             >50                                                             ______________________________________                                    

The results show that compounds of this invention have significantactivity in inhibiting the synthesis of the arachidonic acidlipoxygenase oxidation product 5-HETE.

EXAMPLE 12

The assay of this Example measures the in vivo ability of the compoundsof the invention to inhibit the bronchospasm induced in guinea pigs bythe exogenously administered leukotrienes C₄ and/or D₄. This assay isessentially a measure of the SRS-A antagonist properties of thecompounds tested.

This assay is carried out as follows:

Male Hartley strain guinea pigs (350-600g) are anesthetized withpentobarbital sodium (50 mg/kg, i.p.). The jugular vein is cannulatedfor injection of drugs and the carotid artery for monitoring bloodpressure. The trachea is cannulated for artificial ventilation by aminiature Starling pump and for indirect measurement of respiratoryvolume changes as described infra. Additional pentobarbital sodium (15mg/kg, i.v.) is administered to arrest spontaneous respiration.Submaximal bronchoconstrictor responses are established in controlanimals by varying the dose-levels of leukotriene. Intravenousdose-levels for LTC₄ range from 1 to 2 μg/kg and for LTD₄ the range isfrom 0.3 to 1 μg/kg. The aerosol bronchoprovocation dose for LTC₄ isgenerated from 1.6 μM soution and for LTD₄ from a 2.0 μM solution.

Test drugs are administered either intravenously, by aerosol or orallyat 1 or 10 minutes before induction of bronchospasm by administration ofeither LTC₄ or LTD₄ at the predetermined dose-levels. Aerosols ofsoluble drugs or leukotrienes are produced in-line for 10 seconds onlyby actuation of an ultrasonic nebulizer (Monaghan). Aerosolized drugdosage is expressed in terms of solution concentration and by a fixedaerosol exposure time (approximately 10 seconds). Control animalsreceive saline in place of drug.

Respiratory volume changes are determined by a calibrated piston whosetravel is recorded, via a linear transducer, on a Beckman Dynographrecorder. Maximal bronchoconstrictor volume is determined by clampingoff the trachea at the end of the experiment. Overflow volumes at 5minutes are obtained from the recorded charts.

The overflow volume at 5 minutes is expressed as a percentage of maximalbronchoconstriction. Combined group values are used from each of thesetime intervals to determine the inhibitory effect of drugs. ##EQU2##Students t-test for unpaired data is used to determine statisticalsignificance. Dose response curves are generated and ED₅₀ doses areinterpolated from the regression lines.

Results for a compound of the invention in this assay, using LTD₄ forinduction of bronchospasm, is given below:

                  TABLE II                                                        ______________________________________                                        Compound administered at 10 minutes before induction of                       bronchospasm                                                                                          % Inhibition                                                      Dose        (Statistical Average)*                                Compound of mg/kg       Overflow Volume at                                    Example Number                                                                            ( Intraduodenal)                                                                          5 min.                                                ______________________________________                                        1           50          56.1                                                  7           50          88.7                                                  8           50          90.6                                                  10          50          99.0                                                  ______________________________________                                         *average of 6 experiments                                                

The results show that the compounds of the invention tested havesignificant in vivo activity against LTD₄ induced bronchoconstriction.

What is claimed is:
 1. A compound having the formula: ##STR11## wherein X is --CH₂ CH₂ --,--CH═CH--, ##STR12## R is hydrogen or loweralkyl; R¹ is hydroxy, amino, loweralkyl sulfonamido, perfluoro loweralkyl sulfonamido or OR;R² is hydrogen or loweralkyl; R³ is hydrogen or loweralkyl; or R² and R³ taken together form a benzene ring; and the dotted line represents an optional double bond;and the pharmaceutically acceptable salts thereof.
 2. The compound of claim 1, which is 1,2,3,4-tetrahydro-7-(2-quinolinylmethoxy)-1-naphthalenol.
 3. The compound of claim 1, which is 7-(2-quinolinylmethoxy)-2-naphthalenol.
 4. The compound of claim 1, which is 2-[[(7-methoxy-2-naphthalenyl)oxy]methyl]quinoline.
 5. The compound of claim 1, which is 7-(2-pyridinylmethoxy)-2-naphthalenol.
 6. The compound of claim 1, which is 7-(2-quinolinylmethoxy)-1-naphthalenamine.
 7. The compound of claim 1, which is 7-(2-quinolinylmethoxy)-2-naphthalenamine.
 8. The compound of claim 1, which is N-[7-(2-quinolinylmethoxy)-2-naphthalenyl]ethane sulfonamide.
 9. The compound of claim 1, which is 2-[[(5,6,7,8-tetrahydro-8-methylene-2-naphthalenyl)oxy]methyl]quinoline.
 10. The compound of claim 1, which is N-[7-(2-quinolinyl methoxy)-2-naphthalenyl]trifluoromethane sulfonamide. 